Modulators of IRF4 expression

Abstract

The present embodiments provide methods, compounds, and compositions useful for inhibiting IRF4 expression, which may be useful for treating, preventing, or ameliorating a cancer associated with IRF4.

What is claimed: 
     
       1. A compound comprising a modified oligonucleotide 15 to 30 linked nucleosides in length having a nucleobase sequence comprising at least 15 contiguous nucleobases of the nucleobase sequence of SEQ ID NO: 2021, or a pharmaceutically acceptable salt thereof. 
     
     
       2. The compound of  claim 1 , wherein the modified oligonucleotide comprises a nucleobase sequence of SEQ ID NO: 2021. 
     
     
       3. The compound of  claim 1 , wherein the modified oligonucleotide consists of a nucleobase sequence of SEQ ID NO: 2021. 
     
     
       4. The compound of  claim 1 , wherein the modified oligonucleotide comprises at least one modified internucleoside linkage, at least one modified sugar, or at least one modified nucleobase. 
     
     
       5. The compound of  claim 4 , wherein the modified internucleoside linkage is a phosphorothioate internucleoside linkage. 
     
     
       6. The compound of  claim 4 , wherein the modified sugar is a bicyclic sugar. 
     
     
       7. The compound of  claim 6 , wherein the bicyclic sugar is selected from the group consisting of: 4′-(CH 2 )-O-2′ (LNA); 4′-(CH 2 )2-O-2′ (ENA); and 4′-CH(CH 3 )-O-2′(cEt). 
     
     
       8. The compound of  claim 4 , wherein the modified sugar is 2′-O-methoxyethyl. 
     
     
       9. The compound of  claim 4 , wherein the modified nucleobase is 5-methylcytosine. 
     
     
       10. The compound of  claim 1 , wherein the modified oligonucleotide comprises:
 a gap segment consisting of linked deoxyribonucleotides; 
 a 5′ wing segment consisting of linked nucleosides; and 
 a 3′ wing segment consisting of linked nucleosides; 
 wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment and wherein each nucleoside of each wing segment comprises a modified sugar. 
 
     
     
       11. The compound of  claim 10 , wherein:
 the gap segment consists of ten linked deoxynucleosides; 
 the 5′ wing segment consists of two linked nucleosides; and 
 the 3′ wing segment consists of four linked nucleosides; 
 wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment; wherein each nucleoside of the 5′ wing segment comprises a cEt nucleoside; wherein the 3′ wing segment comprises a cEt nucleoside, a 2′-O-methoxymethyl nucleoside, a cEt nucleoside, and a 2′-O-methoxymethyl nucleoside in the 5′ to 3′ direction; wherein each internucleoside linkage is a phosphorothioate linkage; and wherein each cytosine is a 5-methylcytosine. 
 
     
     
       12. The compound of  claim 1 , wherein the compound is a sodium salt. 
     
     
       13. A composition comprising the compound of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
       14. A method for treating or ameliorating a cancer in an individual comprising administering a composition of  claim 13 . 
     
     
       15. The method of  claim 14 , wherein the cancer is a blood cancer, myeloma, multiple myeloma, B cell malignancy, lymphoma, B cell lymphoma, T cell lymphoma, or leukemia. 
     
     
       16. The method of  claim 14 , wherein the cancer is multiple myeloma. 
     
     
       17. The method of  claim 14 , wherein the composition is administered parenterally.